pterins

Summary

Summary: Compounds based on 2-amino-4-hydroxypteridine.

Top Publications

  1. Alp N, Channon K. Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease. Arterioscler Thromb Vasc Biol. 2004;24:413-20 pubmed
    ..Thus, BH4 represents a potential therapeutic target in the regulation of eNOS function in vascular disease. ..
  2. Gutzke G, Fischer B, Mendel R, Schwarz G. Thiocarboxylation of molybdopterin synthase provides evidence for the mechanism of dithiolene formation in metal-binding pterins. J Biol Chem. 2001;276:36268-74 pubmed
    ..A two-step reaction of MPT synthesis is proposed where the dithiolene is generated by two thiocarboxylates derived from a single tetrameric MPT synthase. ..
  3. Sheng Y, Khanam N, Tsaksis Y, Shi X, Lu Q, Bognar A. Mutagenesis of folylpolyglutamate synthetase indicates that dihydropteroate and tetrahydrofolate bind to the same site. Biochemistry. 2008;47:2388-96 pubmed publisher
    ..This suggests that the 5,10-methylenetetrahydrofolate binding site identified in the L. casei ternary structure may bind diglutamate and polyglutamate folate derivatives. ..
  4. Lake M, Temple C, Rajagopalan K, Schindelin H. The crystal structure of the Escherichia coli MobA protein provides insight into molybdopterin guanine dinucleotide biosynthesis. J Biol Chem. 2000;275:40211-7 pubmed
    ..The binding site for MPT is located adjacent to the GTP-binding site in the C-terminal half of the molecule, which contains another set of conserved residues presumably involved in MPT binding. ..
  5. Pruet J, Jasheway K, Manzano L, Bai Y, Anslyn E, Robertus J. 7-Substituted pterins provide a new direction for ricin A chain inhibitors. Eur J Med Chem. 2011;46:3608-15 pubmed publisher
    ..This makes the discovery of new inhibitors of great importance. We have previously used 6-substituted pterins, such as pteroic acid, as an inhibitor platform with moderate success...
  6. Achari A, Somers D, Champness J, Bryant P, Rosemond J, Stammers D. Crystal structure of the anti-bacterial sulfonamide drug target dihydropteroate synthase. Nat Struct Biol. 1997;4:490-7 pubmed
    ..The 7,8-dihydropterin pyrophosphate (DHPPP) substrate binds in a deep cleft in the barrel, whilst sulfanilamide binds closer to the surface. The DHPPP ligand site is highly conserved amongst prokaryotic and eukaryotic DHPSs...
  7. Graham D, White R. Elucidation of methanogenic coenzyme biosyntheses: from spectroscopy to genomics. Nat Prod Rep. 2002;19:133-47 pubmed
    ..The literature from 1971 to September 2001 is reviewed, and 169 references are cited. ..
  8. Scott J, Rasche M. Purification, overproduction, and partial characterization of beta-RFAP synthase, a key enzyme in the methanopterin biosynthesis pathway. J Bacteriol. 2002;184:4442-8 pubmed
    ..extorquens is the first report of a putative methanopterin biosynthetic gene found in the Bacteria and provides evidence that the pathways of methanopterin biosynthesis in Bacteria and Archaea are similar...
  9. Vladic N, Ge Z, Leucker T, Brzezinska A, Du J, Shi Y, et al. Decreased tetrahydrobiopterin and disrupted association of Hsp90 with eNOS by hyperglycemia impair myocardial ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2011;301:H2130-9 pubmed publisher
    ..The results suggest that eNOS dysregulation may be a central mechanism of impaired cardioprotection during hyperglycemia...

More Information

Publications62

  1. Ormazabal A, Garcia Cazorla A, Fernandez Y, Fernandez Alvarez E, Campistol J, Artuch R. HPLC with electrochemical and fluorescence detection procedures for the diagnosis of inborn errors of biogenic amines and pterins. J Neurosci Methods. 2005;142:153-8 pubmed
    The analysis of biogenic amines (BA) and pterins in cerebrospinal fluid (CSF) is essential for the early diagnosis of neurotransmission defects in the paediatric age...
  2. Mathieu M, Debousker G, Vincent S, Viviani F, Bamas Jacques N, Mikol V. Escherichia coli FolC structure reveals an unexpected dihydrofolate binding site providing an attractive target for anti-microbial therapy. J Biol Chem. 2005;280:18916-22 pubmed
    ..As such, the presence of a folate binding site in E. coli FolC, which is different from the one seen in FPGS enzymes, provides avenues for the design of specific inhibitors of this enzyme in antimicrobial therapy. ..
  3. Hevener K, Yun M, Qi J, Kerr I, Babaoglu K, Hurdle J, et al. Structural studies of pterin-based inhibitors of dihydropteroate synthase. J Med Chem. 2010;53:166-77 pubmed publisher
  4. Moreira W, Leblanc E, Ouellette M. The role of reduced pterins in resistance to reactive oxygen and nitrogen intermediates in the protozoan parasite Leishmania. Free Radic Biol Med. 2009;46:367-75 pubmed publisher
    ..Reduced pterins are known scavengers of reactive oxygen and nitrogen intermediates...
  5. Blaszczyk J, Li Y, Shi G, Yan H, Ji X. Dynamic roles of arginine residues 82 and 92 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: crystallographic studies. Biochemistry. 2003;42:1573-80 pubmed
    ..Two oxidized forms of HP are observed with an occupancy ratio of 0.50:0.50 in the 0.89-A structure. The oxidation of HP has significant impact on its binding to the protein as well as the conformation of nearby residue W89. ..
  6. Dantola M, Denofrio M, Zurbano B, Gimenez C, Ogilby P, Lorente C, et al. Mechanism of photooxidation of folic acid sensitized by unconjugated pterins. Photochem Photobiol Sci. 2010;9:1604-12 pubmed publisher
    ..This process also takes place with other pterins as photosensitizers...
  7. Amour J, Brzezinska A, Jager Z, Sullivan C, Weihrauch D, Du J, et al. Hyperglycemia adversely modulates endothelial nitric oxide synthase during anesthetic preconditioning through tetrahydrobiopterin- and heat shock protein 90-mediated mechanisms. Anesthesiology. 2010;112:576-85 pubmed publisher
    ..Enhancing the production of BH4 may represent a potential therapeutic strategy. ..
  8. Woo H, Hwang Y, Kim Y, Kang J, Choi Y, Kim C, et al. Escherichia coli 6-pyruvoyltetrahydropterin synthase ortholog encoded by ygcM has a new catalytic activity for conversion of sepiapterin to 7,8-dihydropterin. FEBS Lett. 2002;523:234-8 pubmed
    ..The same activity, however, was also detected in a PTPS ortholog of Synechocystis sp. PCC 6803 but not significant in Drosophila and human enzymes, suggesting that the activity may be prevalent in bacterial PTPS orthologs. ..
  9. Grochowski L, Xu H, Leung K, White R. Characterization of an Fe(2+)-dependent archaeal-specific GTP cyclohydrolase, MptA, from Methanocaldococcus jannaschii. Biochemistry. 2007;46:6658-67 pubmed
    The first step in the biosynthesis of pterins in bacteria and plants is the conversion of GTP to 7,8-dihydro-d-neopterin triphosphate catalyzed by GTP cyclohydrolase I (GTPCHI)...
  10. Blaszczyk J, Li Y, Cherry S, Alexandratos J, Wu Y, Shaw G, et al. Structure and activity of Yersinia pestis 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as a novel target for the development of antiplague therapeutics. Acta Crystallogr D Biol Crystallogr. 2007;63:1169-77 pubmed
    ..Therefore, these structural and biochemical data are valuable for the design of novel medical countermeasures against plague. ..
  11. Meininger C, Marinos R, Hatakeyama K, Martinez Zaguilan R, Rojas J, Kelly K, et al. Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency. Biochem J. 2000;349:353-6 pubmed
    ..GTP-cyclohydrolase activity was low because of a decreased expression of the protein in the diabetic cells. ..
  12. Shi G, Blaszczyk J, Ji X, Yan H. Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: synthesis and biochemical and crystallographic studies. J Med Chem. 2001;44:1364-71 pubmed
  13. Dittrich S, Mitchell S, Blagborough A, Wang Q, Wang P, Sims P, et al. An atypical orthologue of 6-pyruvoyltetrahydropterin synthase can provide the missing link in the folate biosynthesis pathway of malaria parasites. Mol Microbiol. 2008;67:609-18 pubmed
  14. Maden B. Tetrahydrofolate and tetrahydromethanopterin compared: functionally distinct carriers in C1 metabolism. Biochem J. 2000;350 Pt 3:609-29 pubmed
  15. Blau N, Bonafe L, Krageloh Mann I, Thony B, Kierat L, Hausler M, et al. Cerebrospinal fluid pterins and folates in Aicardi-Goutières syndrome: a new phenotype. Neurology. 2003;61:642-7 pubmed
    ..To describe three unrelated children with a distinctive variant of Aicardi-Goutières syndrome (AGS) characterized by microcephaly, severe mental and motor retardation, dyskinesia or spasticity, and occasional seizures...
  16. Buchenau B, Thauer R. Tetrahydrofolate-specific enzymes in Methanosarcina barkeri and growth dependence of this methanogenic archaeon on folic acid or p-aminobenzoic acid. Arch Microbiol. 2004;182:313-25 pubmed publisher
    ..The presence of both H4SPT and H4F in M. barkeri is in agreement with earlier isotope labeling studies indicating that there are two separate C1 pools in these methanogens...
  17. Blaszczyk J, Li Y, Wu Y, Shi G, Ji X, Yan H. Essential roles of a dynamic loop in the catalysis of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase. Biochemistry. 2004;43:1469-77 pubmed
    ..The loop plays an important role in the stabilization of the ternary complex and is critical for catalysis. ..
  18. Stammers D, Achari A, Somers D, Bryant P, Rosemond J, Scott D, et al. 2.0 A X-ray structure of the ternary complex of 7,8-dihydro-6-hydroxymethylpterinpyrophosphokinase from Escherichia coli with ATP and a substrate analogue. FEBS Lett. 1999;456:49-53 pubmed
  19. Blaszczyk J, Shi G, Yan H, Ji X. Catalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 A resolution. Structure. 2000;8:1049-58 pubmed
    ..The rigidity of the adenine-binding pocket and hydrogen bonds are responsible for adenosine specificity. The nonconserved residues that interact with the substrate might be responsible for the species-dependent properties of an isozyme. ..
  20. Levy C, Minnis D, Derrick J. Dihydropteroate synthase from Streptococcus pneumoniae: structure, ligand recognition and mechanism of sulfonamide resistance. Biochem J. 2008;412:379-88 pubmed publisher
    ..The results show that binding of DHPPP and pABA are separate distinguishable events in the reaction cycle, and that mutations which confer resistance to sulfonamide drugs act exclusively on the second step in the binding process. ..
  21. Mashhadi Z, Xu H, White R. An Fe2+-dependent cyclic phosphodiesterase catalyzes the hydrolysis of 7,8-dihydro-D-neopterin 2',3'-cyclic phosphate in methanopterin biosynthesis. Biochemistry. 2009;48:9384-92 pubmed publisher
    ..0 mol of zinc and 0.8 mol of iron per protomer. MptB requires Fe(2+) for activity, the same as observed for MptA. Thus the first two enzymes involved in H(4)MPT biosynthesis in the archaea are Fe(2+) dependent...
  22. Wang Q, Hauser V, Read M, Wang P, Hanson A, Sims P, et al. Functional identification of orthologous genes encoding pterin recycling activity in Plasmodium falciparum and Toxoplasma gondii. Mol Biochem Parasitol. 2006;146:109-12 pubmed
  23. White R. Purine biosynthesis in the domain Archaea without folates or modified folates. J Bacteriol. 1997;179:3374-7 pubmed
    ..It is concluded that archaea, which function with modified folates such as MPT, are able to carry out purine biosynthesis without the involvement of folates or modified folates. ..
  24. Hennig M, Dale G, D Arcy A, Danel F, Fischer S, Gray C, et al. The structure and function of the 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Haemophilus influenzae. J Mol Biol. 1999;287:211-9 pubmed publisher
    ..The three-dimensional structure of a binary complex has been refined at 2.1 A resolution. The location of the substrate analog and a sulfate ion gives important insight into the molecular mechanism of the enzyme...
  25. Pannirselvam M, Simon V, Verma S, Anderson T, Triggle C. Chronic oral supplementation with sepiapterin prevents endothelial dysfunction and oxidative stress in small mesenteric arteries from diabetic (db/db) mice. Br J Pharmacol. 2003;140:701-6 pubmed
    ..Furthermore, these results suggest that decreased biosynthesis of BH4 may not be the basis for endothelial dysfunction in SMA from db/db mice...
  26. Egorov S, Krasnovsky A, Bashtanov M, Mironov E, Ludnikova T, Kritsky M. Photosensitization of singlet oxygen formation by pterins and flavins. Time-resolved studies of oxygen phosphorescence under laser excitation. Biochemistry (Mosc). 1999;64:1117-21 pubmed
    ..of photosensitized 1O2 phosphorescence (1270 nm) were performed in air-saturated aqueous ((D2)O) solutions of pterins (2-amino-4-hydroxy-6,7-dimethylpteridine (DMP) and 2-amino-4-hydroxy-6-tetrahydroxybutyl-(D-arabo)pteridine (TOP))..
  27. Rokos H, Beazley W, Schallreuter K. Oxidative stress in vitiligo: photo-oxidation of pterins produces H(2)O(2) and pterin-6-carboxylic acid. Biochem Biophys Res Commun. 2002;292:805-11 pubmed
  28. Baca A, Sirawaraporn R, Turley S, Sirawaraporn W, Hol W. Crystal structure of Mycobacterium tuberculosis 7,8-dihydropteroate synthase in complex with pterin monophosphate: new insight into the enzymatic mechanism and sulfa-drug action. J Mol Biol. 2000;302:1193-212 pubmed
    ..Finally, the Mtb DHPS structure reveals a highly conserved pterin binding pocket that may be exploited for the design of novel antimycobacterial agents. ..
  29. Babaoglu K, Qi J, Lee R, White S. Crystal structure of 7,8-dihydropteroate synthase from Bacillus anthracis: mechanism and novel inhibitor design. Structure. 2004;12:1705-17 pubmed publisher
    ..Finally, as an initial step in the development of pterin-based inhibitors, we present the structure of DHPS complexed with 5-nitro-6-methylamino-isocytosine...
  30. Moheno P, Pfleiderer W, Fuchs D. Plasma cytokine concentration changes induced by the antitumor agents dipterinyl calcium pentahydrate (DCP) and related calcium pterins. Immunobiology. 2009;214:135-41 pubmed publisher
    ..The finding that the novel calcium pterins and CaCl(2)...
  31. Noiriel A, Naponelli V, Gregory J, Hanson A. Pterin and folate salvage. Plants and Escherichia coli lack capacity to reduce oxidized pterins. Plant Physiol. 2007;143:1101-9 pubmed
    ..In trypanosomatid parasites, reduction of such oxidized pterins is crucial for pterin and folate salvage. We therefore sought evidence for this reaction in plants...
  32. Rosentel J, Healy F, Maupin Furlow J, Lee J, Shanmugam K. Molybdate and regulation of mod (molybdate transport), fdhF, and hyc (formate hydrogenlyase) operons in Escherichia coli. J Bacteriol. 1995;177:4857-64 pubmed
    ..Upon entering the cytoplasm, molybdate branches out to mod regulation, fdhF and hyc activation, and metabolic conversion, leading to MGD synthesis and active molybdoenzyme synthesis. ..
  33. Banerjee R, Shane B, McGuire J, Coward J. Dihydrofolate synthetase and folylpolyglutamate synthetase: direct evidence for intervention of acyl phosphate intermediates. Biochemistry. 1988;27:9062-70 pubmed
    ..However, mass spectral analysis of the TMP derived from the mammalian FPGS-catalyzed reactions showed clearly that 18O transfer had occurred. ..
  34. Romao M, Archer M, Moura I, Moura J, LeGall J, Engh R, et al. Crystal structure of the xanthine oxidase-related aldehyde oxido-reductase from D. gigas. Science. 1995;270:1170-6 pubmed
    ..The molybdopterin dinucleotide is deeply buried in the protein. The cis-dithiolene group of the pyran ring binds the molybdenum, which is coordinated by three more (oxygen) ligands. ..
  35. Gorris L, Voet A, van der Drift C. Structural characteristics of methanogenic cofactors in the non-methanogenic archaebacterium Archaeoglobus fulgidus. Biofactors. 1991;3:29-35 pubmed
    ..The levels of the various cofactors were determined in cultures grown either on formate or lactate as the carbon source and sulphate or thiosulphate as the sulphur source. ..
  36. Shen R, Alam A, Zhang Y. Inhibition of GTP cyclohydrolase I by pterins. Biochim Biophys Acta. 1988;965:9-15 pubmed
    b>Pterins inhibit rat liver GTP cyclohydrolase I activity noncompetitively...
  37. Johnson J, Indermaur L, Rajagopalan K. Molybdenum cofactor biosynthesis in Escherichia coli. Requirement of the chlB gene product for the formation of molybdopterin guanine dinucleotide. J Biol Chem. 1991;266:12140-5 pubmed
    ..Wild type cells were shown to contain both molybdopterin and molybdopterin guanine dinucleotide, while cells of chlB mutants were found to contain elevated levels of molybdopterin but no detectable molybdopterin guanine dinucleotide. ..
  38. Iobbi Nivol C, Palmer T, Whitty P, McNairn E, Boxer D. The mob locus of Escherichia coli K12 required for molybdenum cofactor biosynthesis is expressed at very low levels. Microbiology. 1995;141 ( Pt 7):1663-71 pubmed
    ..The mobB gene encodes a polypeptide with a putative nucleotide binding site. All available mob mutations which have been selected for by their ability to grow anaerobically in the presence of chlorate are located in the mobA gene. ..
  39. Chan M, Mukund S, Kletzin A, Adams M, Rees D. Structure of a hyperthermophilic tungstopterin enzyme, aldehyde ferredoxin oxidoreductase. Science. 1995;267:1463-9 pubmed
    ..These properties may contribute to the extreme thermostability of this enzyme...
  40. Gu M, Ye J, Qiu W, Han L, Zhang Y, Gu X. [Mutational analysis of patients with 6-pyruvoyltetrahydrobiopterin synthesis deficiency]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2009;26:183-6 pubmed publisher
    ..The P87S, N52S, D96N and IVS1nt-291A to G mutations are the hot-spots mutations of the PTS gene in Chinese PTPSD patients. Using PCR-RFLP technique to screen the mutations in the PTS gene can increase the efficiency of gene diagnosis. ..
  41. Wheatley N, Sundberg C, Gidaniyan S, Cascio D, Yeates T. Structure and identification of a pterin dehydratase-like protein as a ribulose-bisphosphate carboxylase/oxygenase (RuBisCO) assembly factor in the ?-carboxysome. J Biol Chem. 2014;289:7973-81 pubmed publisher
    ..We conclude that this conserved PCD-like protein, renamed here ?-carboxysome RuBisCO assembly factor (or acRAF), is a novel RuBisCO chaperone integral to ?-carboxysome function. ..
  42. Gramer G, Garbade S, Blau N, Lindner M. Pharmacokinetics of tetrahydrobiopterin following oral loadings with three single dosages in patients with phenylketonuria. J Inherit Metab Dis. 2009;32:52-7 pubmed publisher
    ..Levels of B + P increase significantly with increasing BH(4) doses. There is no correlation between B + P levels and decrease in Phe level. ..
  43. Fekkes D, Voskuilen Kooijman A. Quantitation of total biopterin and tetrahydrobiopterin in plasma. Clin Biochem. 2007;40:411-3 pubmed
    ..1% (w/v) dithiothreitol and waiting for 2-3 h before centrifugation are optimal for adequate quantitation of both pterins. For a reliable determination of tetrahydrobiopterin and total biopterin in plasma, blood tubes must contain a ..
  44. Pangkanon S, Charoensiriwatanamsc W, Liamsuwanmd S. 6-pyruvoyltetrahydropterin synthase deficiency two-case report. J Med Assoc Thai. 2006;89:872-7 pubmed
    ..23 mg/dl and 23.4 mg/dl respectively. The urinary pterins analysis showed low biopterin and high neopterin...
  45. Dumitru R, Ragsdale S. Mechanism of 4-(beta-D-ribofuranosyl)aminobenzene 5'-phosphate synthase, a key enzyme in the methanopterin biosynthetic pathway. J Biol Chem. 2004;279:39389-95 pubmed
    ..60 mm and K(2) = 1.900 mm, under saturated PRPP and varied pABA. Synthase lacks any chromogenic cofactor, and the presence of pyridoxal phosphate and the mechanistically related pyruvoyl cofactors has been strictly excluded. ..
  46. Wright J, Yurasek G, Chen Y, Rosowsky A. Further studies on the interaction of nonpolyglutamatable aminopterin analogs with dihydrofolate reductase and the reduced folate carrier as determinants of in vitro antitumor activity. Biochem Pharmacol. 2003;65:1427-33 pubmed
    ..1 micro M. The IC(50) values of these compounds as inhibitors of the growth of CCRF-CEM cells after 72hr of drug exposure ranged from 0.53 to 55nM, and were qualitatively consistent with the other results. ..
  47. Freisleben A, Schieberle P, Rychlik M. Syntheses of labeled vitamers of folic acid to be used as internal standards in stable isotope dilution assays. J Agric Food Chem. 2002;50:4760-8 pubmed
    ..The mass spectrometric studies confirmed that the compounds could be used as internal standards in stable isotope dilution assays. ..
  48. Fukuzumi S, Kojima T. Control of redox reactivity of flavin and pterin coenzymes by metal ion coordination and hydrogen bonding. J Biol Inorg Chem. 2008;13:321-33 pubmed publisher
  49. Kumar M, Vijayakrishnan R, Subba Rao G. In silico structure-based design of a novel class of potent and selective small peptide inhibitor of Mycobacterium tuberculosis Dihydrofolate reductase, a potential target for anti-TB drug discovery. Mol Divers. 2010;14:595-604 pubmed publisher
    ..78 nM) and is a selective (approximately 120 fold over hDHFR) inhibitor for mtDHFR. Hence, the tripeptide is a suitable lead compound for the development of novel anti-TB drugs. ..
  50. Daubner S, McGinnis J, Gardner M, Kroboth S, Morris A, Fitzpatrick P. A flexible loop in tyrosine hydroxylase controls coupling of amino acid hydroxylation to tetrahydropterin oxidation. J Mol Biol. 2006;359:299-307 pubmed
    ..The V/K(tyr) to V/K(phe) ratios for these variants were altered significantly, but the results did not suggest that F184 of TyrH or Y138 of PheH plays a dominant role in determining amino acid substrate specificity. ..
  51. Kamada Y, Jenkins G, Lau M, Dunbar A, Lowe E, Osawa Y. Tetrahydrobiopterin depletion and ubiquitylation of neuronal nitric oxide synthase. Brain Res Mol Brain Res. 2005;142:19-27 pubmed
    ..Thus, inadequate amounts of tetrahydrobiopterin may lead to a sustained decrease in the steady state level of nNOS that is not readily reversed. ..
  52. Munoz Munoz J, Garcia Molina F, Arribas E, García Ruíz P, Tudela J, García Cánovas F, et al. Suicide inactivation of tyrosinase in its action on tetrahydropterines. J Enzyme Inhib Med Chem. 2011;26:728-33 pubmed publisher
    ..From the results obtained, it can be deduced that the velocity of the inactivation governed by ([Formula: see text]) and the potency of the same ([Formula: see text]) follow the order: BH(4) > MBH(4) > DMBH(4). ..
  53. Abu Ajaj K, El Abadla N, Welker P, Azab S, Zeisig R, Fichtner I, et al. Comparative evaluation of the biological properties of reducible and acid-sensitive folate prodrugs of a highly potent doxorubicin derivative. Eur J Cancer. 2012;48:2054-65 pubmed publisher